Study On Evaluation Model & Method Of Quality For Injection Of Traditional Chinese Medicine Based On Biothermokinetics

Traditional Chinese Medicinal Injection (TCMI) has a popular clinical application. However, it's also the major factor to initiate most of the Adverse Drug Reaction (ADR)/Adverse Drug Event (ADE) of Traditional Chinese Medicine (TCM). To reduce or avoid those hazards and to ensure the safety of clinic medication, we made the foundation of quality control system available as the hot spots and nodus in most of researchs.In this paper, we made the control of quality consistency and stability as a breakthrough, and selected Qingkailing Injection (QKL) as the model drug for our investigation. First the sample library was build through collection and preparation, then based on the routine physics-chemistry examination, routine pharmacological safety examination, and also the chemical analysis(which including chemical characteristic spectrum and determination), we mainly applied biothermokinetics to constructing the bio-assessment of quality evaluation and control on TCMI, in which the bio-thermographs is the core means and index, so as to describe the qualities of all samples qualitatively and quantitatively. In the end, standard database was established based on information of qualified sample, while the sensitive information, which response quality fluctuation and associate with safety, were sieved and the thresholds were set. By pattern recognition and parameter checkout, we could evaluate and control the quality consistency and stability of the injection, which help to detect the quality fluctuation of samples early and quickly, and to predict the potential ADE/ADR for ensuring clinical safety. The main results and conclusion are summarized below:1. Collection, Preparation and Routine Examination of Sample 50 batches of QKL injection were collected or prepared, including 18 bathes of qualified samples, 32 batches of special samples. The routine physical and chemical properties (RPCP) and routine pharmacological safety (RPCS) information of qualified and special samples are examined according to China Pharmacopoeia (ChP).22 batches special samples were detected by both methods, because of visible extraneous or alteration in shade; Only 12 batches of special samples were detected by safety examination, because of the severe deteriorative change. It shows us that the routine examination is not efficiency enough in identification of quality fluctuation.2. Chemical Analysis HPLC-DAD-ELSD was applied to the chemical analysis of QKL injection (including chemical characteristic spectrum and determination).Chemical Characteristic Spectrum (CCS) was established,21 hromatographic peaks were matched as some common peaks. The similarity analysis shows that the similarities of qualified samples were high (0.845～1.000) respectively, indicating that the chemical characteristic spectrum has good applicability; while different batches of special sample matched 16～21 chromatographic peaks with CCS, and the similarity of special samples were 0.705～0.996, indicating that the quality of special samples has changed obviously. The cluster analysis shows that different sorts could be clustered respectively, while some special sample and qualified sample were confounding. The determination of 10 compositions shows different degree of fluctuations in different sample, but the difference between qualified sample and sample of exceed the time limit is not obvious. In all, chemical analysis could detect the quality fluctuation of QKL injection sensitively, which maybe help to control the consistency and stability of quality quantitatively and objectively.3. Study on Bio-assessment Microcalorimetry (MC) was used to build the biothermokinetics graph of all samples, and parameters of BTK were extracted. Because of the graph from staphylococcus aureus (SA) was influenced sensitively by all of the factors, the information is too complicated to analysis, while the Escherichia coli and Tetrahymona thermophila BF5 is not sensitive enough. At last, Blastomyces albicans(CA) was choose as model microbe which could be fit for distinguish all of the samples significantly. The pattern recognition based on CA was applied to performance its discriminative functions as follows:(1) Normal=-1536.21+0.59T²m-674.6P²m-4.56T+1224.34k₂(2) Abnormal=-632.44+1.370T²m-358.92P²m-1.39T+2371.11k₂Thresholds of all parameters from normal and abnormal samples were established, Which help to discriminating between the two.4. Aggregate Analysis The comprehensive analysis show that there is good correlation between chemical analysis and bio-assessment, which could be valid supplement and consummate to quality control system of TCMI. However, it's also help to construct the parameter checkout system, based on the RPCP, Chemical CS, biotical FP, valuable and feasible for prediction on the potential ADR/ADE of TCMI and ensure the safety and effection of clinic medication.